tbuckley/cabot-search huggingface dataset:
Pembrolizumab versus placebo as adjuvant therapy in stage IIB or IIC melanoma: Final analysis of distant metastasis-free survival in the phase 3 KEYNOTE-716 study.
Authors: Jason J. Luke, Paolo Antonio Ascierto, Muhammad Adnan Khattak, Luis de la Cruz Merino, Michele Del Vecchio, Piotr Rutkowski, Francesco Spagnolo, Jacek Mackiewicz, Vanna Chiarion-Sileni, John M. M. Kirkwood, Caroline Robert, Jean-Jacques Grob, Federica de Galitiis, Dirk Schadendorf, Matteo S. Carlino, Larry Wu, Mizuho Fukunaga-Kalabis, Clemens Krepler, Alexander M. Eggermont, Georgina V. Long
Journal: Journal of Clinical Oncology (2023)

LBA9505 Background: Adjuvant pembrolizumab significantly improved distant metastasis-free survival (DMFS) and recurrence-free survival (RFS) in patients with resected stage IIB or IIC melanoma versus placebo. We present the protocol-specified final DMFS analysis from KEYNOTE-716 (NCT03553836). Methods: Eligible patients were ≥12 years old with resected stage IIB or IIC cutaneous melanoma per American Joint Committee on Cancer, 8th edition, guidelines and a negative sentinel lymph node biopsy. In part 1 of the study, patients were randomly assigned (1:1) to pembrolizumab 200 mg (2 mg/kg up to 200 mg for pediatric patients) or placebo every 3 weeks for up to 17 cycles (~1 year) or until disease recurrence, unacceptable toxicity, or withdrawal. Randomization was stratified by T category for adults (T3b vs T4a vs T4b), with a separate stratum for pediatric patients. The primary end point was RFS per investigator review. DMFS per investigator review was a secondary end point. The protocol-specified final DMFS analysis was based on a target of 195 DMFS events. No formal hypothesis testing was performed because DMFS and RFS end points were met at previous interim analyses. The data cutoff date for this analysis was January 4, 2023. Results: Overall, 976 patients were randomly assigned to receive pembrolizumab (n = 487) or placebo (n = 489). Median duration of follow-up (time from randomization to the data cutoff date) was 39.4 months (range, 26.0-51.4). Compared with placebo, adjuvant pembrolizumab improved DMFS (medians: not reached; hazard ratio [HR], 0.59 [95% CI, 0.44-0.79]) and RFS (medians: not reached; HR, 0.62 [95% CI, 0.49-0.79]). The 36-month DMFS rate was 84.4% with adjuvant pembrolizumab versus 74.7% with placebo; the 36-month RFS rate was 76.2% with adjuvant pembrolizumab versus 63.4% with placebo. DMFS benefit with adjuvant pembrolizumab over placebo was observed regardless of cancer stage at baseline (stage IIB HR, 0.62 [95% CI, 0.42-0.92]; stage IIC HR, 0.57 [0.36-0.88]). Similar results were observed with RFS (stage IIB HR, 0.58 [95% CI, 0.43-0.79]; stage IIC HR, 0.65 [95% CI, 0.45-0.94]). No new safety signals were observed. Conclusions: With a median follow-up of 39.4 months, adjuvant pembrolizumab for resected stage IIB and IIC melanoma continued to show DMFS and RFS benefit over placebo, with no new safety signals. Clinical trial information: NCT03553836 .
Intracranial efficacy of sotorasib versus docetaxel in pretreated<i> KRAS</i> G12C-mutated advanced non-small cell lung cancer (NSCLC): Practice-informing data from a global, phase 3, randomized, controlled trial (RCT).
Authors: Anne-Marie C. Dingemans, Konstantinos Syrigos, Lorenzo Livi, Astrid Paulus, Sang-We Kim, Yuanbin Chen, Enriqueta Felip, Frank Griesinger, Kadoaki Ohashi, Gerard Zalcman, Brett Gordon Maxwell Hughes, Jens Benn Sorensen, Normand Blais, Carlos G. M. Ferreira, Colin R Lindsay, Rafal Dziadziuszko, Patrick J. Ward, Cynthia Chinedu Obiozor, Yang Wang, Solange Peters
Journal: Journal of Clinical Oncology (2023)

LBA9016 Background: Brain metastases are common (~30%) in patients (pts) with KRAS G12C-mutated advanced NSCLC and have a negative impact on survival and quality of life (QOL). In the CodeBreaK 200 global, phase 3 RCT, sotorasib was the first oral KRAS G12C inhibitor to show improved progression-free survival (PFS) and overall response rate (ORR), with a better toxicity profile and QOL, compared with intravenous docetaxel in pretreated KRAS G12C-mutated advanced NSCLC. Here we describe the first RCT data evaluating the intracranial (IC) efficacy of sotorasib versus docetaxel from the CodeBreaK 200 study. Methods: Pts with KRAS G12C-mutated advanced NSCLC who progressed after platinum-based chemotherapy and a checkpoint inhibitor were randomized 1:1 to sotorasib (960 mg daily; n=171) or docetaxel (75 mg/m 2 every 3 weeks; n=174). Patients with treated, stable (non-progressing) brain metastases were eligible for study. Baseline brain imaging, by contrast enhanced MRI, was performed for all pts at screening. For pts with history of or brain metastasis at baseline, the brain MRI was repeated at every subsequent imaging assessment (every 6 weeks). A post-hoc analysis on IC efficacy (CNS PFS and time to CNS recurrence) was assessed by blinded independent central review (BICR) per modified Response Assessment in Neuro-Oncology Brain Metastases (mRANO-BM). Systemic response was also assessed by RECIST 1.1. Results: CNS metastases by imaging at baseline were present in 40 pts (23%) in the sotorasib arm and 29 pts (17%) in the docetaxel arm (full analysis set, FAS). With a median follow-up of 20.0 months, the median systemic PFS by RECIST 1.1 in the FAS was 6.1 months versus 4.5 months (HR 0.57 [95% CI: 0.30, 1.07], P=0.045) for sotorasib versus docetaxel, respectively. Time to CNS recurrence in the FAS was 9.6 months with sotorasib versus 5.4 months with docetaxel (HR 0.84 [95% CI: 0.32, 2.19], P=0.37). Treatment-related adverse events of any grade occurred in 77.5% of pts treated with sotorasib versus 89.7% of pts treated with docetaxel. Conclusions: In the first randomized evaluation of IC activity of any KRAS G12C inhibitor, sotorasib demonstrated a reduced risk of progression and trend towards delayed time to CNS recurrence versus docetaxel in patients with pretreated KRAS G12C-mutated advanced NSCLC who had treated, stable brain metastases. These results suggest IC activity with sotorasib to complement the overall PFS benefit observed with sotorasib versus docetaxel. Clinical trial information: NCT04303780 .
Eltrombopag Preserves the Clonogenic Potential of Hematopoietic Stem Cells During Treatment With Antithymocyte Globulin in Patients With Aplastic Anemia
Authors: Margherita Vieri, Benjamin Rolles, Maria Crocioni, Mirle Schemionek-Reinders, Susanne Isfort, Jens Panse, Tim H. Brümmendorf, Fabian Beier
Journal: HemaSphere (2023)

Aplastic anemia (AA) is frequently caused by a T-cell mediated autoimmune depletion of the hematopoietic stem and progenitor cell (HSPC) compartment. Immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and cyclosporine represents the first-line treatment of AA. One side effect of ATG therapy is the release of proinflammatory cytokines such as interferon-gamma (IFN-γ), which is considered a major factor in the pathogenic autoimmune depletion of HSPC. Recently, eltrombopag (EPAG) was introduced for therapy of refractory AA patients due to its ability to bypass IFN-γ-mediated HSPC inhibition among other mechanisms. Clinical trials have evidenced that EPAG started simultaneously with IST leads to a higher response rate compared with its later administration schedules. We hypothesize that EPAG might protect HSPC from negative effects of ATG-induced release of cytokines. We observed a significant decrease in colony numbers when both healthy peripheral blood (PB) CD34 + cells and AA-derived bone marrow cells were cultured in the presence of serum from patients under ATG treatment, as compared with before treatment. Consistent with our hypothesis, this effect could be rescued by adding EPAG in vitro to both healthy and AA-derived cells. By employing an IFN-γ neutralizing antibody, we also demonstrated that the deleterious early ATG effects on the healthy PB CD34 + compartment were mediated at least partially by IFN-γ. Hence, we provide evidence for the hitherto unexplained clinical observation that concomitant use of EPAG in addition to IST comprising ATG leads to improved response in patients with AA.
AB1813-HPR PREVALENCE AND EVOLUTION OF OCCUPATIONAL SHOULDER TENDINITIS OVER A PERIOD OF 10 YEARS IN THE TUNISIAN CENTER REGION
Authors: G. Asma, A. Brahem, A. Chouchen, R. Mejri, I. Kacem, M. Maoua, O. El Maalel, H. Kalboussi, S. Chatti, N. Mrizek
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Shoulder pain is one of the most common regional pain syndromes. Shoulder tendinitis is the second recognized cause of musculoskeletal disorders of the upper limbs after carpal tunnel syndrome. Symptoms can be persistent and disabling in terms of an individual's ability to carry out daily activities both at home and in the workplace with significant and socio-economic costs. <h3>Objectives</h3> To assess the prevalence of occupational tendinitis of the shoulder and its evolution during the study period, and to describe the socioprofessional characteristics of the workers. <h3>Methods</h3> This is a retrospective cross-sectional study of all cases of tendonitis of the rotator cuff, working in the private sector, recognized by the competent medical commission of the National Medical Care Fund of the region of Tunisian center over a period of 10 years. <h3>Results</h3> During the study period, we identified 635 cases of shoulder tendinitis, i.e. 29.5% of all musculoskeletal disorders of the upper limbs. The average age of the population was 44.56 years ± 7.7 years. Our study population was mainly women (82.5%) with a sex ratio of 0.21. The majority of patients worked in the textile sector (76.2% i.e. n= 487) and the electronic sector (4.5% i.e. n= 28). Average seniority of workers in their jobs was ranging from 1 to 36 years. Seamstress (63.4%) and workman (17.7%) were the most affected jobs. The cases of shoulder tendinitis were in continuous rise over the 10 years (p=0.001, r=0.86). <h3>Conclusion</h3> Our study add an evidence to suggest that shoulder disorders may be increased among some workers, particularly those with jobs involving combinations of exposure to: overhead work and repetition. Most of the research on management of shoulder disorders has rarely included occupational outcomes. Adequate and rigorous prevention is essential to reduce the prevalence of this with painful consequences. <h3>References</h3> [1] Ohlsson K, Attewell RG, Johnsson B, et al. An assessment of neck and upper extremity disorders by questionnaire and physical examination. Ergonomics. 1994;37:891–897. [2] Boocock MG, Collier JMK, McNair PJ, et al. A framework for the classification and diagnosis of work-related upper extremity conditions; systematic review. Semin Arth Rheum. 2009;38:289–311. [3] Miranda H, Punnett L, Viikari-Juntura E, et al. Physical work and chronic shoulder disorder. Results of a prospective population-based study. Ann Rheum Dis. 2008;67:218–223. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
AB1687 DOES DISEASE ACTIVITY EXPLAIN HEALTH-RELATED QUALITY OF LIFE IN AXIAL SPONDYLARTHRITIS? A SYSTEMATIC LITERATURE REVIEW
Authors: J. Drouet, B. Fautrel, L. Gossec
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Health-related quality of life (HRQoL) is the ultimate objective of treatment in axial spondylarthritis (axSpA) [1]. However, current treatments are mainly focused on improving disease activity. Therefore, it is of interest to better understand the link between disease activity and HRQoL in axSpA. <h3>Objectives</h3> To explore through a systematic literature review the link between disease activity and HRQoL in axSpA. <h3>Methods</h3> Systematic literature review in December 2022 of articles reporting an association between disease activity and HRQoL in patients with axSpA. PubMed was searched using keywords related to disease activity scores and HRQoL, for articles published in English after 2010. Disease activity was assessed by ASDAS or BASDAI. For HRQoL, we analysed the ASAS Health Index (ASAS-HI) as key outcome. All statistical measures of a potential link between ASDAS and HRQoL were collected; correlations were prioritsed for homogeneity. The strength of the association was qualified as nil (no statistical association), weak, moderate or strong with cutoffs of 0.50 and 0.70 for correlations. No meta-analysis was performed. <h3>Results</h3> Of 122 papers, 23 were relevant, ie, 14375 patients: weighted mean age 42.5 years, weighted mean disease duration 14.3 years, 67.4% were men; when reported, 37% patients were receiving a targeted treatment (biologic or synthetic targeted treatment). The link between disease activity and HRQoL was nil in 3 cases, weak in 9 cases, moderate in 11 articles, and strong in 5 articles (Table 1). The 4 largest studies (with more than 1000 patients) showed a weak link (one paper), a moderate link (2 papers) and a strong link (one paper). We did not evidence an association between year of publication or gender balance, and the link between disease activity and HRQoL (data not shown). <h3>Conclusion</h3> HRQoL is a complex concept which is not only linked to disease activity in axSpA. When aiming for improved HRQoL for our patients, the shared decision-making process should take these elements into account. <h3>Reference</h3> [1]Ramiro S, et al. ASAS-EULAR recommendations for the management of axial spondyloarthritis: 2022 update. Ann Rheum Dis 2022. https://doi.org/10.1136/ard-2022-223296. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Juliette Drouet Grant/research support from: Societe Francaise de Rhumatologie Master Grant, Bruno Fautrel: None declared, Laure Gossec: None declared.
AB1749-PARE IMPACT OF FACIAL SIGNS OF SYSTEMIC SCLEROSIS ON PATIENTS’ SELF-ESTEEM
Authors: Z. Syrine, A. Feki, S. Ben Jemaa, Y. Mabrouk, A. Cyrine, M. Ezzeddine, M. H. Kallel, H. Fourati, R. Akrout, S. Baklouti
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The dimensions of self-concept and body image are essential for assessing the quality of life of individuals with chronic diseases. Systemic sclerosis (SSc) is characterized by facial involvement that can lead to aesthetic changes, functional disability as well as psychological impact. <h3>Objectives</h3> To assess the influence of face involvement on self-esteem in SSc patients. <h3>Methods</h3> A cross- sectional study was carried out on patients followed for Systemic sclerosis at a rheumatology department. Included patients completed the Burden of Face Affected (BoFA) questionnaire as well as the Rosenberg self-esteem scale (RSES). All data was collected after patient consent and was analyzed using the SPSS statistical package. <h3>Results</h3> Forty patients who fulfilled the 2013 ACR/EULAR Classification Criteria for Systemic Sclerosis were included. There were 8 male and 32 female with a sex ratio female to male of 4. The median age was 45 years old [19-71] and median disease duration 1 year. The majority of our patients (85%, n=34) suffered from diffuse form of SSc. 15%(n=6) had a limited form. Fingertip ulcers were observed in 13 patients (32.5%) and telangiectasia in 16 patients (40%). Raynaud's phenomenon was found in 34 patients (85%). Severe organ involvements were detected as interstitial lung disease in 17 patients (42,5%), pulmonary hypertension in 7 patients (17.5%) and renal involvement in 2 patients (5%). Mean (±SD) Rodnan score was 19.6 ± 6.2 and 70% (28 patients) had a limited mouth opening. Mean(±SD) BoFA score was 68±10.3; 0 implying no impact and 100 for major impact of face affection. Mean Rosenberg self-esteem scale was 26.6±3.3 reflecting low self-esteem. Rosenberg self-esteem correlated negatively with BoFA scores r = -0,36; p=0,02 with low levels of self-esteem associated with more face affection symptoms and no significant correlation between RSES and gender, age or Rodnan score. <h3>Conclusion</h3> Patients' perception of their face affection in SSc is poor and can be considered as an important component of patients' self-esteem. Effective interventions need to be directed during follow-up to improve function and satisfaction with body image. <h3>Reference</h3> [1]https://doi.org/10.1016/j.annder.2020.04.023 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
AB1683 VALIDITY AND PSYCHOMETRIC CHARACTERISTICS OF THE DURUÖZ HAND INDEX IN PATIENTS WITH PSORIATIC ARTHRITIS
Authors: M. T. Duruöz, S. Acer Kasman, N. Öz, H. H. Gezer, E. Uzun, K. Nas
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The Duruöz Hand Index (DHI) is a valuable scale developed for evaluating hand functions of patients with rheumatoid arthritis and has subsequently proven to be valid and reliable in various diseases. <h3>Objectives</h3> This study aims to investigate the validity and reliability of DHI in patients with psoriatic arthritis (PsA). <h3>Methods</h3> Patients diagnosed with PsA according to CASPAR criteria were enrolled. The demographic, clinical, and functional characteristics of patients were evaluated. Functional assessment was performed with DHI, Hand Functional Index (HFI), Health Assessment Questionnaire (HAQ), and VAS-disability scale. C-reactive protein level, patients' and physicians' global VAS, swelling and tenderness of the hand joints, gross grip strength and thumb strength, and disease activity assessments were recorded as non-functional parameters related to active disease status. The reliability of DHI was assessed by internal consistency (Cronbach's alpha coefficient). Face, content, and construct validity (convergent and divergent) were evaluated. Face and content validities were assessed via cognitive debriefing interviews with the patients. The correlations of the DHI with HAQ, HFI, and VAS disability were assessed for convergent validity. The correlations of the DHI with DAPSA, BASDAI, MDA, PSAQoL, Jenkins index, PASI, and grip strength were evaluated for divergent validity. <h3>Results</h3> One hundred and forty-four patients (74.3% female) with a mean age of 45.33 (SD: 11.58) years were included in this study. Cognitive debriefing showed the DHI to be clear, understandable, and relevant. It was easy to complete and calculate, with the 4 minutes and 30 seconds, respectively. The Cronbach's alpha coefficient was 0.963, and for the test–retest reliability of the DHI, the intraclass correlation coefficient was 0.904 (p&lt;0.001). DHI showed good correlations with the functional disability scales (HAQ, HFI, VAS-disability), indicating its convergent validity and moderate to non-significant correlations with the non-functional parameters supporting its divergent validity (Table 1). <h3>Conclusion</h3> The DHI is a valid and reliable scale to evaluate the functional disability of hands in patients with PsA. <h3>Reference</h3> [1]Duruöz MT et al. Development and validation of a rheumatoid hand functional disability scale that assesses functional handicap. J Rheumatol 1996; 23:1167-72. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
AB1795-HPR COXITIS IN RHEUMATOID ARTHRITIS: IS THERE ANY CORRELATION BETWEEN CATASTROPHIZING AND FUNCTIONAL DISABILITY?
Authors: O. Hamdi, H. Boussaa, S. Miladi, B. A. Hiba, L. Souabni, K. Ouenniche, S. Kassab, S. Chekili, K. Ben Abdelghani, F. Alia, A. Laatar
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Coxitis is a marker of severity in rheumatoid arthritis (RA) since it is associated with a functional disability. Therefore, it leads to a loss of autonomy with a significant psychological impact. <h3>Objectives</h3> We aimed to assess the correlation between catastrophizing and functional disability associated with rheumatoid coxitis. <h3>Methods</h3> We conducted a cross-sectional study including patients with RA (2010 ACR/EULAR criteria). Clinical, biological and radiological data were collected. RA activity was assessed using the Disease Activity Score (DAS<sub>28</sub> ESR). The quality of life was assessed using the Health Assessment Questionnaire (HAQ). Hip function was assessed using the Lequesne algofunctional index (IAF). Catastrophizing was evaluated by the Pain Catastrophizing Scale (PCS), which is composed of 13 items. PCS total score varies from 0 (no catastrophizing) to 52 (significant tendency to catastrophizing). The correlation between Lequesne IAF and PCS was evaluated using the Spearman test. <h3>Results</h3> We included 80 patients (76 women and 4 men) with an average age of 47±12 years [37-77]. The average age at diagnosis was 29±7.5 years. The mean disease duration was 11±6.2 years. RA was erosive in 90% of cases. Rheumatoid factor and anti-citrullinated peptides antibodies were positive in 83% and 85% of cases, respectively. Seventy-five percent of patients were on corticosteroids with an average dose of 10 mg per day of Prednisone equivalent. All patients were on DMARDs: methotrexate (85%), leflunomide (11.2%), and bDMARDs (37.5%). The mean pain Visual Analog Scale was 5.5 cm. The mean overall patient assessment was 4 cm. The mean number of nocturnal awakenings was 1.5. The mean duration of morning stiffness was 45±7.5 minutes. The mean ESR was 29.4±6. The mean CRP was 19.5± 4.4. The mean DAS<sub>28</sub> ESR was 4.5±2.2. The mean HAQ was 1.2±0.4. The mean PCS was 34±3. Coxitis was noted in 28.7% of patients. It was inaugural in 52.1% of cases and bilateral in 14 cases. The mean coxitis duration was 6.8 years. The mean Lequesne IAF was 10.5±3.2. A statistically significant correlation was noted between Lequesne IAF and PCS (r=0.41; p=0.01). <h3>Conclusion</h3> Our study showed that functional disability associated with rheumatoid coxitis was moderately correlated with catastrophizing. Comprehensive management, taking into account the cognitive behavioural sphere, is thus recommended in RA patients with coxitis. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.